Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.

Abstract

We report a third patient with typical cap myopathy due to a heterozygous TPM3 mutation, confirming the importance of this causal association. The p.R168C TPM3 mutation we identified has been reported in two previous patients. The histological changes associated with this mutation vary widely from typical cap myopathy with near complete type 1 predominance (two patients), to typical congenital fibre-type disproportion without protein inclusions (one patient). We performed 2D-gel electrophoresis using muscle biopsies from two patients with the p.R168C mutation and show that mutant protein accounts for around 50% of alpha-tropomyosin(slow) in sarcomeres, consistent with a dominant negative mechanism of disease pathogenesis.

• Authors: Leigh B Waddell, Michaela Kreissl, Andrew Kornberg, Paul Kennedy, Catriona McLean, Annick Labarre-Vila, Nicole Monnier, Kathryn N North, Nigel F Clarke
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 20 Issue 7 Pg. 464-6 (Jul 2010) ISSN: 1873-2364 [Electronic] England
• PMID: 20554445 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• TPM3 protein, human
• Tropomyosin
• Arginine
• Cysteine

Topics

• Adolescent
• Arginine (genetics)
• Child, Preschool
• Cysteine (genetics)
• Humans
• Male
• Muscle, Skeletal (pathology)
• Muscular Diseases (genetics, metabolism, pathology)
• Mutation (genetics)
• Tropomyosin (genetics, metabolism)